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In this randomized controlled trial, anakinra appears to be an effective and safe treatment for colchicine-resistant FMF.

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A primary mechanism for activation of innate immunity is recognition of damage or pathogen associated molecular patterns by pattern recognition receptors (PRRs). Nucleic acid is a damage associated molecular pattern molecule that when internalized into a monocyte and recognized by intracellular nucleic acid sensing toll like receptors will cause production of type 1 interferon. The process by which DNA or RNA is delivered into the cytosol of monocytes in systemic lupus erythematosus remains incompletely understood, and therapeutic approaches to prevent DNA-mediated monocyte activation are needed. We identified two mechanisms for internalization of DNA by monocytes. IgG-bound DNA was internalized by interacting with Fc gamma receptor IIa, while high-mobility group box-1 protein-bound DNA was internalized by interacting with the receptor for advanced glycation end products. Both pathways contribute to an inflammatory phenotype in monocytes exposed to serum from patients with SLE. Moreover, both of these pathways can be inhibited by a pentapeptide, DWEYS, which is a DNA mimetope. In one instance DWEYS directly competes with DNA for antibody binding and in the other DWEYS binds high-mobility group box-1 and blocks its interaction with RAGE. Our data highlight distinct pathways involved in nucleic acid enters monocytes in SLE, and identify a potential therapeutic to prevent nucleic acid internalization in SLE.

BackgroundProfound vitamin B12 deficiency is a known cause of disease, but the role of low or intermediate levels of B12 in the development of neuropathy and other neuropsychiatric symptoms, as well as the relationship between eating meat and B12 levels, is unclear.ObjectiveThe objective of our study was to investigate the role of low or intermediate levels of B12 in the development of neuropathy and other neuropsychiatric symptoms.MethodsWe used food-related Internet search patterns from a sample of 8.5 million people based in the US as a proxy for B12 intake and correlated these searches with Internet searches related to possible effects of B12 deficiency.ResultsFood-related search patterns were highly correlated with known consumption and food-related searches (ρ=.69). Awareness of B12 deficiency was associated with a higher consumption of B12-rich foods and with queries for B12 supplements. Searches for terms related to neurological disorders were correlated with searches for B12-poor foods, in contrast with control terms. Popular medicines, those having fewer indications, and those which are predominantly used to treat pain, were more strongly correlated with the ability to predict neuropathic pain queries using the B12 contents of food.ConclusionsOur findings show that Internet search patterns are a useful way of investigating health questions in large populations, and suggest that low B12 intake may be associated with a broader spectrum of neurological disorders than previously thought.

Objectives Evidence suggests a possible association between the COVID-19 vaccine and autoimmune disease flares or new onset of various autoinflammatory manifestations, such as pericarditis and myocarditis. The objective of this study was to assess the safety of an mRNA-based BNT162b2 anti-COVID-19 vaccine in individuals with familial Mediterranean fever (FMF), a prototypic autoinflammatory disease. Methods Patients participating in this study fulfilled the criteria for diagnosis of FMF, were older than 18 years, and received at least one dose of the vaccine. Data on baseline characteristics, features of FMF, post-vaccination side effects, and disease flares were acquired using electronic medical files and telephone interviews. Results A total of 273 FMF patients were recruited for the study. More than 95% were vaccinated with two doses of the vaccine. The rates of local reactions following the first and second vaccine doses were 65.5% and 60%, respectively, and 26% and 50.4%, respectively, for systemic adverse events. These rates are lower than those reported for the general population from real-world and clinical trial settings. Postvaccination FMF activity remained stable in most patients. None of the patients reported an attack of pericarditis or myocarditis, considered the most serious vaccine-associated adverse events. Patients with a more active FMF disease and patients harboring the M694V mutation had a significantly higher rate of post-vaccination systemic side effects and attacks. Conclusion The BNT162b2 mRNA Covid-19 vaccine is safe in patients with FMF. Our results support the administration of this vaccine to FMF patients according to guidelines applicable to the general population.

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